Revision:B-cells and humoral immunity

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B-cells are produced in the bone marrow and are distributed through the body in the lymph nodes. B-cells respond to the 'foreign' antigens of a pathogen by producing specific antibodies. Antibodies are complex proteins that are released into the blood and carried to the site of infection. B-cells do not fight pathogens directly.

An antibody, or immunoglobulin, is a y-shaped protein molecule that is made by a B-lymphocyte in response to a particular antigen. Antibodies interact with the antigen and render it harmless. When a pathogen tries to invade the body for the first time, each of its antigens activates B-cell, which divides rapidly to produce a large population of cells. All the new cells are identical: we say they are clones, and they all secrete antibodies specific for the invading pathogen. When the infection is over, most of the newlymade B-cells die. This sequence of events is the primary immune response.

So that the body can respond more quickly next time, some of the activated B-cells persist in the body for several years. These memory cells 'remember' what the pathogen is like and, if it tries to invade again, they all divide rapidly to produce an even greater number of active B-cells, all capable of secreting specific antibody. This response is called a secondary immune response and is very much quicker and more effective than the primary response.

B-cell

• B Cell Receptors bind soluble antigens (like diphtheria toxoid, the protein introduced into your body in the DTP vaccine)
• the bound antigen molecules are engulfed into the B cell by receptor-mediated endocytosis
• the antigen is digested into fragments which
• are then displayed at the cell surface nestled inside a class II histocompatibility molecule
• Helper T cells specific for this structure (i.e., with complementary TCRs) bind the B cell and
• secrete lymphokines that:
  • stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into a clone of cells with identical BCRs
  • switch from synthesizing their BCRs as integral membrane proteins to a soluble version
  • differentiate into plasma cells that secrete these soluble BCRs, which we now call antibodies.

T-cells and cell-mediated immunity

T-cells respond to specific antigens. When a pathogen first infect the body, each individual antigen stimulates a single t-cell. This divides to form a clone, in the same way that B-cells do. Som of the activated t-cells become memory cells and persist in the body, ready to mount a secondary response if the pathogen attaks again. The others, however, do not produce antibodies. They develop further to become either helper T-cells, Killer T-cells or suppressor T-cells.

The surface of each T cell also displays thousands of identical T cell receptors (TCRs). The TCR binds a bimolecular complex displayed at the surface of some other cell called an antigen-presenting cell (APC). This complex consists of:

• a fragment of an antigen lying within the groove of a
• histocompatibility molecule.

Most of the T cells in the body belong to one of two subsets. These are distinguished by the presence on their surface of one or the other of two glycoproteins designated:

CD4 - CD4⁺ T cells bind an epitope consisting of an antigen fragment lying in the groove of a class II histocompatibility molecule. CD4⁺ T cells are essential for both the cell-mediated and antibody-mediated branches of the immune system:

Cell-mediated immunity

These CD4⁺ cells bind to antigen presented by antigen-presenting cells (APCs) like phagocytic macrophages and dendritic cells. The T cells then release lymphokines that attract other cells to the area. The result is inflammation: the accumulation of cells and molecules that attempt to wall off and destroy the antigenic material (an abscess is one example, the rash following exposure to poison ivy is another).

Antibody-mediated immunity

These CD4⁺ cells, called helper T cells, bind to antigen presented by B cells (as shown above). The result is the development of clones of plasma cells secreting antibodies against the antigenic material.

CD8 - The best understood CD8⁺ T cells are cytotoxic T lymphocytes (CTLs). They secrete molecules that destroy the cell to which they have bound. This is a very useful function if the target cell is infected with a virus because the cell is usually destroyed before it can release a fresh crop of viruses able to infect other cells.

Every time you get a virus infection, say influenza (flu), the virus invades certain cells of your body (in this case cells of the respiratory passages). Once inside, the virus subverts the metabolism of the cell to make more virus. This involves synthesizing a number of different macromolecules encoded by the viral genome.

In due course, these are assembled into a fresh crop of virus particles that leave the cell (often killing it in the process) and spread to new target cells.

Except while in transit from their old homes to their new, the viruses work inside of your cells safe from any antibodies that might be present in blood, lymph, and secretions.

But early in the process, infected cells display fragments of the viral proteins in their surface class I molecules. CTLs specific for that antigen will be able to bind to the infected cell and often will be able to destroy it before it can release a fresh crop of viruses.

In general, the role of the CD8⁺ T cells is to monitor all the cells of the body, ready to destroy any that express foreign antigen fragments in their class I molecules.

Which of these molecules is present determines what types of cells the T cell can bind to.

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